S4: Development of quantitative AOPs

Open discussion on the challenges in development of quantitative AOPs
Open discussion on the challenges in development of quantitative AOPs, OpenTox Euro 2016

Hristro Aladjov


ENV/EHS, OECD, Paris, France


Consultant: co-leading the OECD, JRC, EPA AOP-KB project
Associate Professor: Institute of Biophysics and Biomedical Engineering, Sofia, Bulgaria


The growing interest in Adverse Outcome Pathways (AOP) as pragmatic organizing principle of existing toxicological information has produced a broad range of research ideas from practical rules how to build AOPs to their use as part of networks for predictive purposes.

There are several aspects of the AOPs development however that relay on evaluation of evidences, which remains not entirely objective and well documented process. The need for transparent explanation of the rationale behind the use of particular evidence becomes even more apparent when building quantitative AOPs, since different data interpretations are possible depending on the assumptions used.

To focus the discussion we would like to address the following questions: 1) how to establish causality in quantitative terms and what kind of experiments can be utilized to support it 2) do all stressor types are created equal in the design of quantitative experiments to study (key) event relationships 3) is it possible and desirable to describe the normal and perturbed biology with the same dynamic models 4) how to estimate the quantitative contribution of each upstream cause if more than one is leading to a (key) event  5) should AOPs allow (key) event relationships that go backwards in level of biological organization.

While the talk will present the solutions available in Effectopedia software for some of the challenges the need for open discussion in the wider AOP community is recognized.